Integrated microtomography and optical imaging systems

ABSTRACT

An integrated microtomography and optical imaging system includes a rotating table that supports an imaging object, an optical stage, and separate optical and microtomography imaging systems. The table rotates the imaging object about a vertical axis running therethrough to a plurality of different rotational positions during a combined microtomography and optical imaging process. The optical stage can be a trans-illumination, epi-illumination or bioluminescent stage. The optical imaging system includes a camera positioned vertically above the imaging object. The microtomography system includes an x-ray source positioned horizontally with respect to the imaging object. Optical and x-ray images are both obtained while the imaging object remains in place on the rotating table. The stage and table are included within an imaging chamber, and all components are included within a portable cabinet. Multiple imaging objects can be imaged simultaneously, and side mirrors can provide side views of the object to the overhead camera.

TECHNICAL FIELD

The present invention relates generally to systems and methods forobtaining multiple types of images of an object, and more particularlyto obtaining such images without transferring the object betweendifferent imaging systems.

BACKGROUND

There are currently numerous non-invasive imaging techniques that can beused to produce images of a given object. Such techniques includeX-rays, magnetic resonance imaging (“MRI”), computed tomography (“CT” or“microtomography”) scans, ultrasound and optical imaging usingstructured light, among others. In addition, various non-invasiveoptical imaging techniques such as bioluminescence and fluorescence canbe used to produce optical images of animal objects, such as in theareas of medical research, pathology, drug discovery and development,and the like. Each such imaging technique has advantages anddisadvantages that are useful for different imaging applications. Sometechniques are well suited to provide spatial or anatomical informationfor internal parts, while others are more suited to provide functionalinformation for an activity of interest within an object being imaged.Due to the differing advantages of different types of imaging systems,it has become increasingly desirable to combine the outputs andstrengths of multiple imaging systems for a single imaging object.

As one particular example of a multi-modal imaging system, there can bea considerable synergistic advantage to combining x-ray microtomography(also known as computed tomography or CT) imaging and optical tomographyto increase the information content of the optical measurements of agiven imaging object. In particular, the morphological informationobtained by microtomography provides anatomical information that assiststhe interpretation of the optical data and improves the model for lighttransport that is required to reconstruct the light source distribution.

Performing optical diffuse tomography reconstruction generally requiresa measurement of the surface topography of a three-dimensional imagingobject. Previous systems to accomplish such reconstructions haveutilized an optical structured light technique to scan the surface ofthe imaging object and produce a surface mesh. This method often workswell, but is limited by complexities like rough fur or dark colors on agiven imaging object. Furthermore, the structured light typically onlygives the surface topography on the top half of the imaging object.Thus, there can be several inherent drawbacks to some multi-modalimaging systems, at least with respect to those that use structuredlight as one of the imaging modes.

Furthermore, a single imaging object is often transferred betweendifferent imaging systems in many traditional multi-modal imagingsystems, such as a combination of x-ray and optical systems. As might beexpected, however, the transfer of an imaging object can result invarious problems with coordinating the different object images. Imagingobject transfer issues can include, for example, jostling or bumping bythe person or apparatus moving the object between disparate imagingsystems. Further problems can arise where the imaging object is a livinganimal or specimen, such as a mouse, that would ordinarily be inclinedto move on its own during the transfer. Substantial changes in imagingobject positioning, muscle flexing and the like during a transferbetween imaging systems can then result in images from the second and/orsubsequent imaging systems that do not overlap well with images from thefirst and/or prior imaging systems. Efforts to combine such disparatesystems into a single imaging system are quite difficult, due to thedifferent requirements, mechanisms and other items that tend tointerfere with each other.

While many systems and methods for providing multiple types of images ofa object have generally worked well in the past, there is always adesire to provide new and improved ways to obtain such internal images.In particular, what is desired are systems and methods that can producemultiple types of images of an imaging object without any need totransfer the object between separate imaging systems.

SUMMARY

It is an advantage of the present invention to provide systems andmethods that produce multiple types of images of an imaging objectwithout any need to transfer the object between separate imagingsystems. Such transfer-less, multi-modal imaging systems can be providedby way of a single imaging system that is adapted to provide twodifferent kinds of imaging on the same imaging object at the samelocation. In particular, such a single imaging system can includefacilities for x-ray imaging and optical tomography in a single locationfor a single imaging object, which can be rotated to a plurality ofdifferent positions at that single location. Specific applications caninvolve the x-ray imaging being done with respect to one axis, and theoptical tomography being done with respect to a different axis that isorthogonal to the x-ray axis. Such configurations allow the multipleimaging modalities to co-exist without interfering with one another,while at the same time enabling a low-cost, compact and portableinstrument.

In various general embodiments, a multi-modal imaging system can includea stage adapted to support a separate imaging object at a singlelocation during a multi-modal imaging process, an optical imaging systemconfigured to obtain optical imaging data on the imaging object whilethe imaging object is on the stage, and a secondary imaging systemseparate from said optical imaging system and configured to obtainsecondary imaging data while the imaging object is on the stage. Theoptical imaging data and the secondary imaging data can both be obtainedwhile the imaging object remains at the single location. Also, theoptical imaging data can be obtained with respect to a first axisrunning through the imaging object, and the secondary imaging data canbe obtained with respect to a second axis running through the imagingobject, where the second axis is orthogonal with respect to the firstaxis.

In various detailed embodiments, the secondary imaging system can be anx-ray imaging system, such as a microtomography imaging system. Further,the first axis can be vertical with respect to the imaging object whilethe second axis is horizontal with respect to the imaging object. Thestage can include transillumination components adapted totransilluminate the imaging object from below. The stage can also oralternatively include a rotating table adapted to support and to rotatethe imaging object to a plurality of different rotational positionsduring the multi-modal imaging process. The secondary imaging system canthen be configured to obtain secondary imaging data for the imagingobject at each of the plurality of different rotational positions. Therotating table can be adapted to support a plurality of separate imagingobjects thereupon, and the optical and secondary imaging systems can beadapted to image the plurality of separate imaging objectssimultaneously.

In still further detailed embodiments, the system can include aprocessing device in logical communication with the both the opticalimaging system and the secondary imaging system, with the processingdevice being adapted to combine imaging data obtained by the opticalimaging system with imaging data obtained by the secondary imagingsystem. An imaging chamber can also be included, and all items can becontained within an outer cabinet that is adapted to contain the stage,the optical imaging system and the secondary imaging system therewithin.Such a cabinet can be readily portable from one location to another.Further detailed embodiments can include one or more mirrors positionedat one or more sides of the imaging object and arranged at an angle withrespect to the stage, table or object, such that one or more side viewsof the imaging object are reflected upward toward the camera.

In various further embodiments, an integrated microtomography andoptical imaging system can include an imaging chamber adapted to containa separate imaging object therewithin, a rotating table located withinthe imaging chamber and adapted to support the imaging object thereupon,and a separate microtomography imaging system. The rotating table can beadapted to rotate the imaging object about a vertical axis runningtherethrough to a plurality of different rotational positions during acombined microtomography and optical imaging process. The opticalimaging system can include a camera positioned substantially verticallyabove the imaging object and adapted to obtain optical images of theimaging object with respect to the vertical axis while the imagingobject is on the rotating table. The microtomography imaging system canbe include an x-ray source and one or more x-ray sensors adapted toreceive x-rays from the x-ray source, with the x-ray source beingpositioned in a substantially horizontal direction with respect to theimaging object on the rotating table. Both the optical images and thex-ray images can be obtained while the imaging object remains within theimaging chamber.

In various detailed embodiments, the multi-modal imaging system caninclude a trans-illumination system adapted to facilitatetransillumination of the imaging object from below, can include anepi-illumination system adapted to facilitate epi-illumination of theimaging object from above, and/or can be adapted to facilitate thebioluminescent imaging of the imaging object. In addition, one or morebeam shaping devices can be situated proximate the x-ray source andadapted to shape an x-ray beam emitted therefrom.

The system can also include a processing device in logical communicationwith both the optical imaging system and the microtomography imagingsystem, with the processing device being adapted to combine imaging dataobtained by the optical imaging system with imaging data obtained by themicrotomography imaging system. Such combination of imaging data fromthe optical and microtomography imaging systems can result in athree-dimensional representation of the separate imaging object. Stillfurther, the entire integrated microtomography and optical imagingsystem can be readily portable from one location to another, such aswhere the entire system is contained within a cabinet having wheelsthereon.

In further detailed embodiments, the processing device can be furtheradapted to process x-ray imaging data obtained from the microtomographyimaging system to yield a volumetric three-dimensional rendering of theimaging object, segment the x-ray imaging data to determine an x-raysurface mesh of the imaging object, map optical image data obtained fromthe optical imaging system onto the x-ray surface mesh of the imagingobject, and process the surface-mapped optical image data through adiffuse tomography algorithm to determine a three-dimensionaldistribution of light-emitting sources within the imaging object. Theprocessing device can also be further adapted to determine an anatomicalmap of tissues within the imaging object using the volumetricmicrotomography data, and create a heterogeneous tissue property map foruse within the optical diffuse tomography algorithm using the anatomicalmap.

Also, the rotating table can be adapted to support a plurality of miceor other separate imaging objects thereupon, and both the opticalimaging system and the microtomography imaging system can be adapted toimage the plurality of separate imaging objects simultaneously. Inaddition, one or more mirrors can be positioned at one or more sides ofthe imaging object or objects and arranged at an angle with respect tothe rotating table such that one or more side views of the imagingobject or objects are reflected upward toward the camera.

In still further embodiments, various methods of imaging a separateimaging object by multiple different imaging systems can include theprocess steps of placing the separate imaging object atop a rotatingtable adapted to support the imaging object at a single location duringa multi-modal imaging process, obtaining one or more optical images ofthe imaging object while the imaging object is atop the rotating table,activating a secondary imaging system, obtaining one or more secondaryimages of the imaging object while the imaging object remains atop therotating table and the secondary imaging system is activated, androtating the rotating table about a vertical axis running therethroughto a plurality of different rotational positions during the imagingprocess. In particular, the one or more optical images can be obtainedalong a first direction with respect to the imaging object, while thesecondary imaging system is located and captures images of the imagingobject in a direction that is orthogonal with respect to the firstdirection. In some embodiments, the secondary imaging system comprises amicrotomography imaging system. The method can also includetransilluminating the imaging object from below while the imaging objectremains atop the rotating table. In addition, the one or more opticalimages can be combined with the one or more secondary images using aprocessing device in logical communication with both the optical imagingsystem and the secondary imaging system.

Other apparatuses, methods, features and advantages of the inventionwill be or will become apparent to one with skill in the art uponexamination of the following figures and detailed description. It isintended that all such additional systems, methods, features andadvantages be included within this description, be within the scope ofthe invention, and be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The included drawings are for illustrative purposes and serve only toprovide examples of possible structures and arrangements for thedisclosed inventive systems and methods for obtaining images of animaging object using different imaging systems at a single location.These drawings in no way limit any changes in form and detail that maybe made to the invention by one skilled in the art without departingfrom the spirit and scope of the invention.

FIG. 1A illustrates in block diagram format an exemplary multi-modalimaging system adapted to provide multiple different modes of imagingfor a given imaging object.

FIG. 1B illustrates in front perspective view an exemplary opticalimaging system adapted to produce a 2-D or 3-D representation withrespect to a given imaging object.

FIG. 2A illustrates a simplified pictorial of diffusive lightpropagation through and out from an imaging object.

FIG. 2B illustrates an exemplary schematic of transillumination of animaging object.

FIG. 3 illustrates in side cross-sectional view an exemplary integratedmicrotomography and optical imaging system according to one embodimentof the present invention.

FIG. 4A illustrates in side cross-sectional view the stage portion ofthe imaging system of FIG. 3 according to one embodiment of the presentinvention.

FIG. 4B illustrates in side perspective view the stage portion of theimaging system of FIG. 3 according to one embodiment of the presentinvention.

FIG. 5 illustrates in side perspective view an exemplary x-ray sourceand plurality of beam shapers according to one embodiment of the presentinvention.

FIGS. 6A-6B illustrate in top perspective views an exemplary integratedmicrotomography and optical imaging system adapted to image multipleimaging objects simultaneously according to one embodiment of thepresent invention.

FIG. 7 illustrates in top perspective view an exemplary integratedmicrotomography and optical imaging system having side mirrors adjacentto the imaging object according to one embodiment of the presentinvention.

FIG. 8 presents a flowchart of an exemplary method of imaging an imagingobject by multiple different imaging systems according to one embodimentof the present invention.

DETAILED DESCRIPTION

Exemplary applications of apparatuses and methods according to thepresent invention are described in this section. These examples arebeing provided solely to add context and aid in the understanding of theinvention. It will thus be apparent to one skilled in the art that thepresent invention may be practiced without some or all of these specificdetails. In other instances, well known process steps have not beendescribed in detail in order to avoid unnecessarily obscuring thepresent invention. Other applications are possible, such that thefollowing examples should not be taken as limiting.

In the following detailed description, references are made to theaccompanying drawings, which form a part of the description and in whichare shown, by way of illustration, specific embodiments of the presentinvention. Although these embodiments are described in sufficient detailto enable one skilled in the art to practice the invention, it isunderstood that these examples are not limiting; such that otherembodiments may be used, and changes may be made without departing fromthe spirit and scope of the invention.

The invention relates in various embodiments to a multi-modal imagingsystem adapted to take and process different types of images of animaging object while the object remains at the same location. Such animaging object can be an animal, such as a mouse or other lab animal,and can be sedated or otherwise alive during the imaging processes. Ofcourse, other imaging objects can also be similarly used in a systemthat is the same or substantially similar to that which is disclosedherein, and it is contemplated that any and all such suitablealternative imaging objects can also be used. In a particular detailedexample, such as that which is provided herein for purposes ofillustration, such a multi-modal imaging system can include an opticalimaging system and a microtomography or other x-ray based imagingsystem, although other types of imaging systems may also be used.

Such a system using x-ray imaging can be preferable to structured lightbased systems, since the x-ray imaging works regardless of fur or colorconditions, and also has the benefit of giving the complete surface ofthe imaging object. Such improvements lead to improved diffuse opticaltomography reconstructions, and this arrangement can be accomplishedusing the various components and techniques disclosed herein.

Introduction

Referring first to FIG. 1A, an exemplary multi-modal imaging systemadapted to provide multiple different modes of imaging for a separateimaging object is shown in block diagram format. Multi-modal imagingsystem 1 comprises a first imaging system 10, a second imaging system20, and at least one processing device 5 adapted to control one or moreof the imaging systems, and/or to process together multiple imagesobtained from the different imaging systems. While the present inventionis primarily described herein with respect to combining data from twoimaging systems, multi-modal imaging system 1 may include more than twoimaging systems, and the illustrative embodiment is not meant to limitthe number of imaging systems that are so combined. Details of amulti-modal imaging system are described in commonly owned U.S. Pat. No.7,190,991 entitled “Multi-Mode Internal Imaging,” which is incorporatedherein in its entirety and for all purposes.

First imaging system 10 and second imaging system 20 can both employ anyone of a variety of imaging modes, and each imaging system 10, 20preferably uses a mode of imaging that is different that the otherimaging system(s) in multi-modal imaging system 1. Exemplary imagingsystems include, for example, various light imaging systems such asphotographic, bioluminescent, and/or fluorescent imaging systems, aswell as other types of imaging systems, such as MRI systems, CT systems,CAT scan systems, X-ray systems, ultrasound systems, nuclear medicineimaging systems such as positron emission tomography (“PET”) systems,single photon emission computed tomography (“SPECT”) systems, amongother possible imaging systems.

First imaging system 10 and second imaging system 20 may produce spatialand/or functional information. Spatial information refers to informationthat contributes to a 2-D (pictorial) or 3-D geometric description ofthe object or its internal portions. A spatial representation provides auser with a 2-D or 3-D pictorial reference of the specimen. A 3-Dgeometric description typically comprises a reconstruction manufacturedby processing data from multiple 2-D images. Functional informationrefers to information that contributes an item or activity of interestwithin the object. In one embodiment, one of the included imagingsystems produces a 2-D or 3-D representation of a bioluminescent lightsource inside a mouse. The bioluminescent source may correspond to awide variety of physiological issues being tracked or tested within themouse, such as progress tracking of a particular cancer within a mouse,or activation of a specific gene. Some imaging applications includeanalysis of one or more representations of light emissions from internalportions of a specimen superimposed on a spatial representation of thespecimen. The luminescence representation indicates portions of aspecimen where an activity of interest may be taking place.

FIG. 1B illustrates in front perspective view an exemplary opticalimaging system adapted to produce a 2-D or 3-D representation withrespect to an imaging object. Optical imaging system 40, which cancorrespond to first imaging system 10 from FIG. 1A, may be used for avariety of imaging tasks, including the capture of photographic,luminescent and structured light images. Optical imaging system 40 canbe, for example, a light imaging system that involves the capture of lowintensity light—often on the order of about 10³ to about 10¹⁰photons/second/centimeter squared/steradian—from a light-emittingobbject. The low intensity light may be emitted from any of a variety oflight sources about or within the imaged object. For example, the lightsource may correspond to luciferase expressing cells within a livingspecimen, such as a mouse. The light source indicates portions of thesample, such as traced molecules in a particular portion of a livingspecimen, where an activity of interest may be taking place. As will bereadily appreciated, such light imaging can involve bioluminescentimaging, fluorescent imaging, and/or any other suitable type of imaging.

As shown, light imaging system 40 can include an imaging chamber 42adapted to receive a light-emitting sample in which low intensity lightis to be detected. A high sensitivity camera 44, such as an intensifiedor a charge-coupled device (“CCD”) camera, can be coupled with theimaging chamber 42. Camera 44 can be capable of capturing luminescent,photographic (i.e., reflection based images) and structured light imagesof an imaging object within imaging chamber 42. A computer 46 and itsinclusive processor 5 working with light imaging system 40 may performprocessing and imaging tasks such as obtaining, analyzing andmanipulating 2-D or 3-D light source representations. An imageprocessing unit 48 optionally interfaces between camera 44 and computer46, and can be used to help generate composite images, such ascombination photographic and luminescent images.

Light imaging systems 40 suitable for use with the present invention areavailable from Caliper Life Sciences of Hopkinton, Mass. Several lightimaging systems suitable for use with the present invention aredescribed in commonly owned U.S. Pat. No. 7,113,217 entitled “Multi-ViewImaging Apparatus,” which is incorporated by reference herein for allpurposes. 3-D imaging systems suitable for use with the presentinvention are further described in commonly owned U.S. Pat. No.7,616,985 entitled “Method and Apparatus for 3-D Imaging of InternalLight Source,” which is also incorporated by reference herein for allpurposes. Various approaches to generating compositephotographic/luminescence images, such as might be desired from theforegoing systems are described in U.S. Pat. No. 5,650,135 issued toContag et al. on Jul. 22, 1997, which is incorporated herein in itsentirety and for all purposes.

Moving next to FIG. 2A, a simplified pictorial 50 of diffusive lightpropagation through and out from an imaging object is provided. Imagingobject 2 can be, for example, a mouse or other mammal. Mouse 2 caninclude one or more internal probes 3, which produce light thatpropagates through and out of the mouse. Internal probe 3 generallyrefers to any object or molecule that produces light, such asfluorescent or bioluminescent light. In the case of fluorescence,internal probe 3 absorbs incident energy of a certain wavelength orwavelength range and, in response, emits light energy at a differentwavelength or wavelength range. In some embodiments, internal probe 3can emits low-intensity fluorescent light. For example, a low intensityfluorescent probe of the present invention can emit light within mouse 2in the range of about 10⁴ to about 10¹⁴ photons/second, depending onprobe concentration and excitation light intensity. For some imagingsystems, a fluorescent probe 3 that emits flux in the range of about 10⁴to about 10¹⁰ photons/second is suitable, while other light fluxes arealso permissible.

Animal tissue is a turbid medium, such that photons are both absorbedand scattered as they propagate through tissue. Photons 7 from internalprobe or source 3 scatter and travel through tissue in the mouse 2 toone or more surfaces 9. The light emitted from the surface 9 may then bedetected by a camera, such as CCD camera 44 from an optical imagingsystem.

Continuing with FIG. 2B an exemplary schematic of transillumination ofan imaging object is provided. In general, transillumination provideslight from a side of an imaging object 2 that is opposite the camera 44(e.g., incident light from below and a camera above), or into a portionof the object not visible to the camera, such that excitation andemission light cumulatively travels through the mouse or other imagingobject. This can result in lower levels of autofluorescence and improvedefficiency of excitation. Also, the ability to move thetransillumination point, relative to a fluorescent probe fixed withinthe animal, provides additional information that can be used for 3Dtomographic reconstructions.

As shown, the excitation light source can include a lamp 90 thatprovides light that passes through a filter 91 in excitation filterwheel 92, which allows a user to change the wavelength band of incidentexcitation light by changing which filter intercepts the incomingexcitation light. The excitation light can be directed along fiberbundle or cable 95 towards a bottom surface of the mouse 2, wheretransillumination light 6 is then projected onto the mouse. In oneembodiment, the outlet position of path 95 can be moved or re-directedto create multiple incident excitation light locations oftransillumination path 95. Light can then propagate through the mouse 2and be detected by camera 44. Although particular arrangements fordiffusive light propagation and transillumination have been shown forpurposes of illustration, it will be readily appreciated that othersuitable arrangements can also be used. Further, it will be readilyappreciated that other optical imaging types and systems can also beused with the multi-modal imaging systems disclosed herein. For example,epi-illumination of the imaging object 2 can be used, which can involvethe use of an epi-illumination system or arrangement. One particularexample of such an ep-illumination system arrangement can be found atcommonly owned U.S. patent application Ser. No. 11/844,920, entitled,“Spectral Unmixing for In-Vivo Imaging,” which is incorporated herein inits entirety and for all purposes. Bioluminescent imaging can also beundertaken.

Integrated Imaging Systems

In addition to the foregoing exemplary types of optical imaging systems,it is specifically contemplated that additional types of imaging also beprovided in the same integrated system. In particular, integratedmulti-modal imaging systems are provided that permit multiple types ofimages of an imaging object without any need to transfer the objectbetween separate imaging systems. That is, in addition to an optical orother first type of imaging, a second type of imaging is also providedat the same location as the first type of imaging. Such a second type ofimaging can be provided by, for example, a microtomography or otherx-ray imaging system.

Turning now to FIG. 3, an exemplary integrated microtomography andoptical imaging system according to one embodiment of the presentinvention is illustrated in side cross-sectional view. Integrated system100 can include imaging components to facilitate both optical imagingand microtomography imaging. Optical imaging components can include, forexample, trans-illumination hardware 170 located beneath a tablesupporting an imaging object, and a camera 144 located above the imagingobject along a vertical axis or distance 148, among other possiblecomponents. Microtomography components can include, for example, anx-ray source 180 and one or more x-ray receptors or sensors, such asx-ray flat panel 182, among other possible components.

The imaging object, stage, table and other various components can all beincluded within an imaging chamber 162, while the chamber, its contentsand all of the other integrated system items and components can becontained within an outer cabinet 160. Outer cabinet 160 can alsoinclude an upper portion 164 adapted to house various optical systemcomponents, such as the camera, its power source and/or its controller.Outer cabinet 160 can also include one or more wheels or coasters 166such that the cabinet, and thus the entire system, can be readilyportable.

Moving now to FIGS. 4A and 4B, a close up of the stage portion of theimaging system of FIG. 3 is shown in side cross-sectional and sideperspective views respectively. Depicted in FIGS. 4A and 4B areessentially the contents of imaging chamber 162, as well as variousimaging components. An imaging object 2 can be placed atop a rotatingtable 172 that can be part of an overall stage adapted to support theimaging object. The stage can be situated above transilluminationhardware 170, if that form of illumination is used, which hardware maybe considered as part of the overall stage. In the event thattransillumination is not desired, then different hardware or equipmentthat supports epi-illumination can alternatively be used. Table 172 canbe adapted to rotate about a vertical axis 148 running therethrough, andan associated camera (not shown) can be situated above the rotatingtable along this vertical axis. One or more bearings 174 can be used topermit ease of rotation for the table 172 with respect to the rest ofthe overall stage.

As noted above, a secondary imaging system can include an x-ray typeimaging system having an x-ray source 180 and an x-ray flat panel 182 orother x-ray detection component or array. A shutter 184 can be used tofacilitate and control the incidence of x-rays from the source 180 toand through the imaging object 2 as it remains atop the table 172. Asshown, the actual location of the x-ray source 180 can be spaced apartfrom and substantially horizontal with respect to the imaging object 2,such that a general incident direction 188 of the emitted x-ray beam issubstantially horizontal or otherwise orthogonal with respect to thevertical axis 148.

As will be readily appreciated, a typical x-ray source 180 can tend toemit x-rays in a broad range of directions. Such an indiscriminateemission of x-rays, however, may cause some problems in a compactmulti-modal imaging system, particularly where excess x-rays may damageand/or interfere with optical imaging equipment or illuminationequipment, which can also lead to reflection and unwanted x-ray noise atthe x-ray sensors. Turning next to FIG. 5, an exemplary x-ray source andplurality of x-ray beam shapers are illustrated in side perspectiveview. X-ray source 180 can be designed to emit x-rays from a sideopening therefrom, whereupon the x-rays would ordinarily propagate inall directions. Instead of allowing this, one or more beam shapingdevices can be used to limit the direction of the emitted x-ray beam,such that the x-rays pass through the object of interest, but aresubstantially above the hardware supporting the object.

Alternatively, or in addition to the simple shutter noted above, aplurality of beam shaping devices 185, 186, 187 can be used to block andshape the emitted x-ray beam. Such beam shaping devices 185, 186, 187can be formed from any suitable x-ray blocking material, such as copper,for example. These devices can be sized, shaped and placed in such asway that the resulting x-ray beam 189 is shaped and directed in a mannerthat delivers a full amount of x-rays to and through the imaging object,but limits the amount of stray x-rays that could cause problemselsewhere within the multi-modal imaging system. As shown, beam shaper185 generally limits the emitted x-rays into a cone shape in thedirection of the imaging object. Beam shaper 186 can then be designed tofurther limit the cone, while beam shaper 187 can be designed to cut offthe unneeded bottom portion of the cone that would extend below therotating table and into any stage equipment, trans-illumination hardwareand the like. Such a bottom cutoff can be at general incident horizontaldirection 188, as shown. It will be readily appreciated that more orfewer beam shaping devices can be used, as may be desired for aparticular design.

In addition to one or more beam shaping devices 185, 186, 187, a filterwheel 190 can be used to further limit or modify the emitted x-ray beam189. One or more filters can be suitably installed within filter wheel190, and the filter wheel can be driven by a motor 192 or otherautomated wheel adjusting device, as will be readily appreciated.

It is worth noting that that the substantially horizontal direction andlocation of the of the x-ray source, x-ray sensors, and x-ray beams withrespect to the imaging object allows for the microtomography imaging toproceed unimpaired by the stage, rotating table, and anytransillumination hardware that might be located underneath the imagingobject, as well as the camera and other optical equipment located abovethe imaging object. In this type of arrangement using optical and x-rayimaging systems that are arranged along perpendicular or otherwiseorthogonal axes, two disparate types of imaging systems can be combinedto image simultaneously and effectively imaging objects at a singlelocation. Of course, a given imaging object can be rotated to aplurality of different positions at the same single location, such aswhere a rotating table is used.

Although the figures show an optical imaging system arranged about avertical axis and an x-ray imaging system arranged about a horizontalaxis or field of view, it will be readily appreciated that the varioushardware components can be rearranged to support reverse or alternateversions of such orthogonal axis that will also work well.

Due to the combined nature of integrated microtomography and opticalimaging system 100, multiple different modes of imaging can be obtainedwith respect to an imaging object without needing to move the imagingobject from system to disparate system. This advantageously avoids manyof the problems that can be associated with imaging object transferbetween systems. This also results in a more reliable and streamlinedcoordination of multiple imaging processing, as it can thus be knownthat images taken by both systems are on the same object as it is in thesame object pose and position and/or rotational position of thesupporting table.

In addition, the ability of the two different modes of imaging tooperate together within a confined space results in a relatively compactsystem that can be assembled into a single portable outer housing orcabinet. This can be accomplished at least in part due to the orthogonalnature of the axes or directions of image taking with respect to the twoor more different imaging systems. That is, where a combined systemmight provide for multi-modal imaging of an object along the same orparallel axes or directions, such an arrangement tends to be cumbersomeand require a substantial amount of space. Conversely, the juxtapositionof disparate imaging equipment along orthogonal axes results in a morecompact and efficient arrangement, which permits the ready portabilityof the integrated imaging system. Furthermore, the arrangement of thetwo disparate imaging systems along perpendicular or orthogonal axesresults in little to no interference between the various hardwarecomponents of the microtomography or x-ray imaging system and thecamera, illumination components and other hardware of the opticalimaging system. This particular arrangement also results in no need fora large and expensive rotational gantry, such as that which is found inmany traditional CT systems.

Additional features and benefits that can be realized through the use ofthe foregoing system are reflected in the alternative embodiments andfeatures presented in FIGS. 6A, 6B and 7. Turning first to FIGS. 6A-6Ban exemplary integrated microtomography and optical imaging systemadapted to image multiple imaging objects simultaneously is illustratedin different top perspective views. As shown, integrated imaging system150 can be identical or substantially similar to system 100 disclosedabove. In particular, integrated imaging system 150 can similarlyinclude imaging components to facilitate both optical imaging andmicrotomography imaging, such as, for example, a camera 144 and otheroptical imaging system components, an x-ray source 180, an x-ray flatpanel or detector 182, and a rotating table 172, among other possibleitems.

Due to this particular choice of imaging technologies and theirrespective arrangements, the system can be adapted to image a pluralityof imaging objects at the same time, as show with respect to imagingobjects 2 and 3. Although imaging objects 2 and 3 are illustrated as twomice that are arranged side by side atop rotating table 172, it will bereadily appreciated that the same technologies and arrangement can beused to image other types of imaging objects as well. As shown, theoptical imaging system can readily capture one or more overhead imagesof the plurality of imaging objects 2, 3, while the microtomographyimaging system can readily capture a series of x-ray images of theimaging objects at different rotational positions of the rotating table172. Provided a sufficient number of x-ray images at differentrotational positions are taken, the associated processing device orsystem can then be adapted to correlate and juxtapose the respectiveoptical and x-ray imaging data such that three-dimensionalreconstructions of both imaging objects 2, 3 can be provided. In thismanner, multiple imaging objects can be imaged using multiple disparatetypes of imaging systems simultaneously, such that useful and accuratethree-dimensional reconstructions of all imaging objects can be providedin an efficient process.

FIG. 7 illustrates in top perspective view an exemplary integratedmicrotomography and optical imaging system having side mirrors adjacentto the imaging object according to one embodiment of the presentinvention. As will be readily appreciated, many imaging objects can havelength to width ratios that are not 1:1. This can result in loss ofspace inefficiencies where a rotating table is used. In addition, theuse of an overhead camera as the only optical system camera can resultin images that are limited in nature. These issues can be overcome byplacing one or more side mirrors adjacent to the imaging object, whichis accomplished in the improved system shown in FIG. 7.

Similar to the foregoing embodiments, integrated imaging system 200 caninclude imaging components to facilitate both optical imaging andmicrotomography imaging, such as, for example, an optical stage (notshown), a camera and other optical imaging system components 240, anx-ray source 280, an x-ray flat panel or detector 282, and a rotatingtable 272, among other possible items. A mouse or other suitable imagingobject 2 can be placed at or near the center of the rotating table 272,and one or more side viewing mirrors 230 can be located proximate theimaging object. Such mirrors 230 can be located on the rotating tableitself, as shown, or may be positioned off of the rotating table, ifdesired. Preferably, mirrors 230 can be designed such that side views ofthe imaging object are reflected upward to the overhead camera and otheroptical system components 240. In this case, three images of imagingobject 2 are projected upward, representing overhead and two side views.

As shown, two triangular shaped and self-supporting mirrors 230 may bepositioned atop the rotating table. Alternatively, other shapes, sizesand mirror arrangements can be used as well. Such a side mirror ormirrors 230 can be arranged at about a 45 degree angle with respect tothe horizontally oriented rotating table 272, such that the side viewsof the imaging object 2 are projected upward in a direct verticaldirection. Of course, adjustments in the angle of the mirrors can bemade where such adjustments are preferable due to the exact positioningof the overhead camera. In the event that the camera is not directlyoverhead or is positioned at some other location, the angles of the sidemirrors 230 can be adjusted accordingly.

In addition, mirrors 230 are preferably formed entirely from materialsthat are transparent to or otherwise non-interfering with x-rays. Suchmaterials can be, for example, low density glass or plastic, along witha non-metallic ink or other dark backing on the back surface tofacilitate reflection. In this manner, the mirrors 230 do notsignificantly interfere with the x-ray source 280 and detector 282 asthe rotating table 272 rotates to its plurality of different positions.

Image Processing

As noted above with respect to FIG. 1, one or more processing devices 5or systems can be used to process together multiple images and/or dataobtained from different imaging systems. Such processing can includeperforming optical diffuse tomography reconstruction for an imagingobject or objects, with such reconstruction involving the combination ofoptical and x-ray data. Various examples of and techniques for using aprocessing device or system to perform the relatively complex types ofreconstruction required for such systems can be found at, for example,commonly owned U.S. Pat. No. 7,190,991 entitled “Multi-Mode InternalImaging,” U.S. Pat. No. 7,599,731 entitled “Fluorescent LightTomography,” U.S. Pat. No. 7,616,985 entitled “Method and Apparatus for3-D Imaging of Internal Light Sources,” and U.S. patent application Ser.No. 11/844,551, entitled, “Apparatus and Methods for Determining OpticalTissue Properties,” each of which is incorporated herein in its entiretyand for all purposes.

It is specifically contemplated that use of processing to combine imagesand/or data from a combined multi-modal optical and x-ray imaging systemcan involve a processing device or system that is in logicalcommunication with both the optical imaging system and themicrotomography or other x-ray imaging system. Such a processing deviceor system can be adapted to combine imaging data obtained by the opticalimaging system with imaging data obtained by the microtomography imagingsystem by using techniques that involve:

-   -   processing x-ray imaging data obtained from the microtomography        or other x-ray imaging system to yield a volumetric        three-dimensional rendering of the imaging object,    -   segmenting the x-ray imaging data to determine an x-ray surface        mesh of the imaging object,    -   mapping optical image data obtained from the optical imaging        system onto the x-ray surface mesh of the imaging object, and    -   processing the surface-mapped optical image data through a        diffuse tomography algorithm to determine a three-dimensional        distribution of light-emitting sources within the imaging        object.

In addition to the above listed techniques, the processing device orsystem can be further adapted to provide additional functionalities thatare specialized with respect to the combination of optical imaging dataand microtomography imaging data. In particular, such additionalspecialized functionalities that can be provided by way of such aprocessing device or system can include:

-   -   determining an anatomical map of tissues within the imaging        object using the volumetric microtomography data, and    -   creating a heterogeneous tissue property map for use within the        optical diffuse tomography algorithm using the anatomical map.        It is worth noting that the function of determining an        anatomical map of tissues within the imaging object can be of        great use where microtomography imaging is used rather than        structured light or other forms of imaging in order to create a        surface mesh of the imaging object.        Method of Use

Turning lastly to FIG. 8, a flowchart of an exemplary method of imagingan imaging object by using multiple different imaging systems isprovided. While the provided flowchart may be comprehensive in somerespects, it will be readily understood that not every step provided isnecessary, that other steps can be included, and that the order of stepsmight be rearranged as desired by a given device manufacturer, vendor oruser. For example, step 306 may alternatively be performed after orsimultaneously with steps 310-314. As another example, step 308 could beperformed before or simultaneously with steps 304 and 306. Also, step304 can be optional, and may be replaced with one or more other forms ordirections of object illumination. Other suitable potential orders ofsteps will be readily appreciated.

After start step 300, process step 302 can involve placing the imagingobject on a rotating table. Again, the rotating table can be adapted tosupport the imaging object at a single location during an integratedmulti-modal imaging process, and the imaging object can be a mouse orother mammal. The imaging object can then optionally be transilluminatedfrom below while it is on the rotating table at process step 304.Although the term “below” has been used, it will be readily appreciatedthat the transillumination should take place at a location by theimaging object that is opposite the location of an associated camera. Assuch, if the camera might be located below the imaging object, then thetransillumination should be made from above the object. In the eventthat transillumination is not used, it will be readily appreciated thatepi-illumination and/or bioluminescence of the imaging object can bealternatively performed for process step 304.

One or more optical images of the object can then be obtained at processstep 306. Obtaining the optical images can take place while the objectis being transilluminated, epi-illuminated and/or is emittingbioluminescence. Also, the optical images can be obtained along a firstdirection with respect to the imaging object. In some embodiments, thiscan be a vertical direction, such as where a camera is positioned abovethe imaging object. Where the rotating table rotates about a verticalaxis running therethrough, it will be readily appreciated that theimages are obtained substantially about such a vertical axis. Of course,it may not be necessary to rotate the horizontally oriented table inorder to obtain one or more optical images from the camera locatedvertically above the imaging object, as will be readily appreciated.

At process step 308, a secondary imaging system can be activated. Asnoted above, such a secondary imaging system can be a microtomography orother suitable x-ray imaging system. In such cases, activating thesecondary imaging system can involve turning on an x-ray source. Thisx-ray source (or other imaging source should a different secondaryimaging system be used) can be located in a direction that is orthogonalwith respect to the first direction. In some embodiments, this directioncan be substantially horizontal with respect to the imaging object.

An x-ray or other secondary image of the object can then be obtained atprocess step 310. In the event of x-ray imaging, this can involve theuse of an array of x-ray sensors positioned proximate the imaging objectand opposite the x-ray source. As in the case of the optical imaging,the image is obtained while the imaging object remains atop the rotatingtable. At subsequent decision step 312, an inquiry is then made as towhether the secondary imaging is finished. If not, then the methodcontinues to step 314, where the table is rotated to a new position.From step 314, the method reverts to step 310, where another secondaryimage is obtained. This cycle repeats until the inquiry result is yes atstep 312.

When the inquiry result is yes, then the method continues to processstep 316, where the optical and secondary imaging results are combinedusing a processing device. The method then ends at end step 318.

Although the foregoing invention has been described in detail by way ofillustration and example for purposes of clarity and understanding, itwill be recognized that the above described invention may be embodied innumerous other specific variations and embodiments without departingfrom the spirit or essential characteristics of the invention. Certainchanges and modifications may be practiced, and it is understood thatthe invention is not to be limited by the foregoing details, but ratheris to be defined by the scope of the appended claims.

What is claimed is:
 1. An integrated microtomography and optical imaging system, comprising: an imaging chamber adapted to contain a separate imaging object therewithin; a rotating table located within the imaging chamber and comprising a surface configured to directly contact and support the separate imaging object so that a length of a body of the object extends in a plane defined by the surface of the rotating table, wherein the rotating table is further adapted to rotate the imaging object about an axis extending through the object in a direction orthogonal to the plane defined by the surface, to a plurality of different rotational positions during a combined microtomography and optical imaging process; an optical imaging system located within or about the imaging chamber, said optical imaging system comprising: a camera positioned substantially vertically above the imaging object in a direction parallel to the axis and adapted to obtain optical images of the imaging object with respect to the axis while the imaging object is on the rotating table; and a radiation source oriented to perform transillumination of the imaging object along a direction parallel to the axis and on a side of the object vertically below the imaging object, so that the optical images correspond to light emitted from the imaging object along the direction parallel to the axis; and a microtomography imaging system located within or about the imaging chamber and configured to obtain x-ray images of the imaging object while the imaging object is in direct contact with the surface of the rotating table, said microtomography imaging system comprising an x-ray source and one or more x-ray sensors adapted to receive x-rays from the x-ray source, wherein the x-ray source is oriented so that x-rays generated by the x-ray source propagate in a direction parallel to the plane defined by the surface, and wherein the optical images and the x-ray images are both obtained while the imaging object remains within the imaging chamber.
 2. The integrated microtomography and optical imaging system of claim 1, wherein said optical imaging system is adapted to facilitate bioluminescent imaging of the imaging object.
 3. The integrated microtomography and optical imaging system of claim 1, further comprising a processing device in logical communication with the optical imaging system and in logical communication with the microtomography imaging system, wherein the processing device is adapted to combine imaging data obtained by the optical imaging system with imaging data obtained by the microtomography imaging system.
 4. The integrated microtomography and optical imaging system of claim 3, wherein said processing device is further adapted to: process x-ray imaging data obtained from the microtomography imaging system to yield a volumetric three-dimensional rendering of the imaging object; segment the x-ray imaging data to determine an x-ray surface mesh of the imaging object; map optical image data obtained from the optical imaging system onto the x-ray surface mesh of the imaging object; and process the surface-mapped optical image data through a diffuse tomography algorithm to determine a three-dimensional distribution of light-emitting sources within the imaging object.
 5. The integrated microtomography and optical imaging system of claim 4, wherein said processing device is further adapted to: determine an anatomical map of tissues within the imaging object using the volumetric microtomography data; and create a heterogeneous tissue property map for use within the optical diffuse tomography algorithm using the anatomical map.
 6. The integrated microtomography and optical imaging system of claim 1, wherein the entire integrated microtomography and optical imaging system is portable from one location to another.
 7. The integrated microtomography and optical imaging system of claim 1, wherein the surface of the rotating table is adapted to directly contact and support a plurality of separate imaging objects thereupon, and wherein the optical imaging system and the microtomography imaging system are both adapted to image the plurality of separate imaging objects simultaneously.
 8. The integrated microtomography and optical imaging system of claim 7, wherein the plurality of separate imaging objects include two or more mice arranged side by side on the rotating table.
 9. The integrated microtomography and optical imaging system of claim 1, further comprising one or more mirrors positioned at one or more sides of the imaging object, wherein said one or more mirrors are arranged at an angle with respect to the rotating table such that one or more side views of the imaging object are reflected upward toward the camera.
 10. The integrated microtomography and optical imaging system of claim 1, further comprising one or more beam shaping devices situated proximate said x-ray source and adapted to shape an x-ray beam emitted therefrom.
 11. A method of imaging an imaging object by multiple different imaging systems, comprising: placing the imaging object in direct contact with a surface of a rotating table so that the surface supports the imaging object at a single location during a multi-modal imaging process, wherein a length of a body of the object extends in a plane defined by the surface of the rotating table; obtaining one or more optical images of the imaging object while the imaging object is in direct contact with the surface of the rotating table; activating a secondary imaging system aligned along a second direction that is orthogonal with respect to the first direction; obtaining one or more secondary images of the imaging object while the imaging object is in direct contact with the surface of the rotating table and the secondary imaging system is activated; and rotating the rotating table about an axis extending through the rotating table and the object in a direction orthogonal to the plane defined by the surface, to a plurality of different rotational positions during the imaging process, wherein the one or more optical images are obtained by: transilluminating the imaging object along a direction parallel to the axis and on a first side of the object; and detecting radiation emitted from the object and propagating along the direction parallel to the axis on a second side of the object opposite the first side.
 12. The method of claim 11, further comprising combining the one or more optical images with the one or more secondary images using a processing device in logical communication with both the optical imaging system and the secondary imaging system.
 13. A multi-modal imaging system, comprising: a stage comprising a rotating table comprising a surface configured to directly contact and support an imaging object so that a length of a body of the object extends in a plane defined by the surface of the rotating table, and to rotate the imaging object during a multi-modal imaging process so that an axis of rotation of the stage extends through the object in a direction orthogonal to the plane defined by the surface; an optical imaging system configured to obtain optical imaging data on the imaging object while the imaging object is on the stage, wherein the optical imaging data is obtained by transilluminating a first side of the imaging object along a first axis extending through the imaging object in a direction parallel to the axis of rotation, and detecting radiation emitted from a second side of the object opposite the first side and propagating along the first axis extending through the imaging object; and a secondary imaging system separate from said optical imaging system and configured to obtain secondary imaging data while the imaging object is on the stage, wherein the optical imaging data and the secondary imaging data are both obtained while the imaging object is in direct contact with the surface of the rotating table, and wherein the secondary imaging data is obtained by measuring radiation along a second axis running through the imaging object, said second axis being orthogonal with respect to said first axis, wherein the stage is further adapted to support the imaging object at a single location relative to the optical and secondary imaging systems during the multi-modal imaging process.
 14. The multi-modal imaging system of claim 13, wherein said secondary imaging system is an x-ray based microtomography imaging system.
 15. The multi-modal imaging system of claim 13, wherein the imaging object is elongated and comprises a body axis extending in a longitudinal direction of elongation of the object, wherein said first axis is oriented in a direction that is perpendicular to a plane comprising the body axis, and said second axis is oriented in a direction that is coplanar with the body axis.
 16. The multi-modal imaging system of claim 13, wherein said rotating table is adapted to rotate the imaging object to a plurality of different rotational positions at the single location during the multi-modal imaging process.
 17. The multi-modal imaging system of claim 16, wherein said secondary imaging system is configured to obtain secondary imaging data for the imaging object at each of the plurality of different rotational positions.
 18. The multi-modal imaging system of claim 16, wherein the surface of the rotating table is adapted to directly contact and support a plurality of separate imaging objects thereupon, and wherein the optical imaging system and the secondary imaging system are both adapted to image the plurality of separate imaging objects simultaneously.
 19. The multi-modal imaging system of claim 13, further comprising a processing device in logical communication with the optical imaging system and in logical communication with the secondary imaging system, wherein the processing device is adapted to combine imaging data obtained by the optical imaging system with imaging data obtained by the secondary imaging system.
 20. The multi-modal imaging system of claim 13, further comprising one or more mirrors positioned relative to the stage so that when the imaging object is supported by the stage, the mirrors are located at one or more sides of the imaging object, wherein said one or more mirrors are arranged at an angle with respect to the stage such that one or more side views of the imaging object are reflected toward a detector of the optical imaging system. 